Secondary structure model

AL Delcher, S Kasif, HR Goldberg, WH Hsu. Protein secondary structure modelling with probabilistic networks. Intelligent Systems m Molecular Biology 1 109-117, 1993. 

The knowledge of the primary structure was the basis for the construction of models of the secondary structure of the RNA molecules. Different approaches have been used in several laboratories to get experimental support for developing secondary structure models for example, chemic modification of the RNA, treatment with single- or double-strand-specihc nucleases, intramolecular RNA cross-linking, isolation and sequence analysis of double-stranded RNA, and, last but not least, comparison of ribosomal RNA sequences from different organisms (reviewed by Brimacombe et al., 1983). 

NMR and kinetic studies have been conducted with the hope of providing more details about the position and conformation of the polypeptide substrate in cAMP-dependent protein kinase. These have served to narrow down the possible spatial relationships between enzyme bound ATP and the phosphorylated serine. Thus, a picture of the active site that is consistent with the available data can be drawn (12,13,66,67). Although these studies have been largely successful at eliminating some classes of secondary polypeptide structure such as oi-hellces, 6-sheets or an obligatory 6-turn conformation 66), the precise conformation of the substrate is still not known. The data are consistent with a preference for certain 6-turn structures directly Involving the phosphorylated serine residue. However, they are also consistent with a preference or requirement for either a coil structure or some nonspecific type of secondary structure. Models of the ternary active-site complexes based on both the coil and the, turn conformations of one alternate peptide substrate have" been constructed (12). These two models are consistent with the available kinetic and NMR data. 

Figure 29-2 (A) Secondary structure model for the 1542-residue E. coli 16S rRNA based on comparative sequence analysis.733 Dots indicate G U or A G pairs dashes indicate G C or A U pairs. Strongly implied tertiary interactions are shown by solid green lines. Helix numbering according to Brimacombe. Courtesy of Robin Gutell. (B) Simplified schematic drawing of type often used. (C) Positions of the A, P, and E sites on the 30S ribosomal subunit from Carter et al7° (D) Stereoscopic view of the three-dimensional fold of the 16S RNA from Thermus thermophilus as revealed by X-ray structural analysis at 0.3 nm resolution. Features labeled are the head (H), beak (Be), neck (N), platform (P), shoulder (Sh), spur (Sp), and body (Bo). (E-H) Selected parts of the 16S RNA. In (E) and (F) the helices are numbered as in (A). (F) and (H) are stereoscopic views. The decoding site...

Figure 29-17 Partial sequence and secondary structure model of RNA of bacteriophage MS2. The initiation and termination codons for each of the three genes (A protein, coat protein, and replicase) are enclosed in boxes as is the second stop signal that is in-frame for the A protein gene but out-of-frame for the coat protein gene. The entire coat protein gene is shown but less them one-third of the entire sequence is given. From W. Fiers and associates.499-501...

Recently, information concerning protein locations within the 30S subunit has been combined with a secondary structure model of 16S rRNA and the location of protein binding sites in rRNA to generate a partial three-dimensional picture of where the rRNA and proteins are situated in this ribosomal subunit (fig. 28.7). 

Recall that the secondary-structure model for RNA is a model - and a crude one at that. It neglects pseudo knots and other tertiary interactions, does not take deviations from the additive nearest neighbor energy model into account, and is based on thermodynamic parameters extracted from melting experiments by means of multidimensional fitting procedures. Thus, you cannot expect perfect predictions for each individual sequence. Rather, the accuracy is on the order of 50% of the base pairs for the minimum free energy structure. 

Fig. 4.11. Secondary structure model tor the 5 halt of the nLSU of Schistosoma mansoni. This is based on the conservation diagram for yeast, Saccharomyces cerevisiae in Ben Ali et at (1999) and the helix numbering of Wuyts et al. (2001a).

Homopolypeptides provide useful secondary structural models for spectroscopic studies on proteins and the ROA spectra of poly(L-lysine) in the three most important conformers are shown in Fig. 7.4. Poly(L-lysine) at alkaline pH... 

Figure 4.2 The hammerhead and hairpin ribozymes. Secondary structures for both the hammerhead and hairpin ribozymes are depicted. N=any nucleotide, R=Purine and Y=Pyrimidine. A diagram of the tertiary structure of the hammerhead ribozyme is depicted above the secondary structure model. The corresponding stems I, II and III in both structures are shown. In the hammerhead ribozyme H=A, C or U at the cleavage site. In the hairpin ribozymes HI, H2, etc. refer to the helical regions of the RNA structure.

In addition to the high sequence homology of these carriers, secondary structure models based on hydropathy analysis (Amara and Kuhar, 1993) are virtually superimposable. All have been assigned 12 transmembrane domains and each transporter is considered to have a large extracellular glycosylated loop between transmembrane domains three and four. 

Most of the studies of the ability of neutral evolution to discover new phenotypes have been carried out on RNA secondary structure models. Here, the neutral network is defined as a connected region of sequence... 

Ruschak AM, Mathews DH, Bibillo A, Spinelli SL, Childs JL, Eickbush TH, Turner DH. Secondary structure models of the 3 untranslated regions of diverse R2 RNAs. RNA 2004 10(6) 978-987. 

Ihckwell DS, Hunqihies Ml, Brass A A secondary structure model of the integrin a subunit N-terminal domain based on analysis of multiple alignments. Cell Adhesion Common 2 385-402,1994. 

One important experimental result was available, the quantitative measurement of the fraction of each secondary structural element by circular dichroism (CD) on purified lipid-protein complexes. This provided a constraint that allowed a careful evaluation of the secondary structure predictions derived from the various approaches, some of which were developed for water-soluble proteins and therefore of uncertain reliability for proteins in a lipid environment. The data from these analyses were combined using an integrated prediction method to arrive at a consensus secondary structure model for each protein. The integrated method involved 36 steps, with independent predictions at each step. The final model was based on an evaluation of the various predictions, with judicious intervention by the authors. As an aid to developing the appropriate weighting of all the data, they carried out the analysis for apoE-3 without reference to the available crystal structure (Wilson et al., 1991), then used the known structure of the HDL-binding amino-terminal domain of apoE-3 as feedback to reevaluate the weighting. 

Fig. 4.7. Illustration of an RNA footprint experiment, (a) Autoradiogram showing the altered chemical and ribonuclease reactivities in the presence (+) and in the absence (-) of a binding protein. The extension is from an end-labelled primer, (b) Reactivites which are altered in the presence of the protein is indicated on a secondary structure model. Protein induced protection of RNase T1 and T2 are indicated by arrows outside the backbone, while arrows penetrating the backbone indicate sites protected against CVE. Bases protected against DMS (circles), ke-thoxal (stars) and CMCT (boxed residues) are indicated. The small vertical arrows indicate enhanced base reactivities.

Examples of models that have been proposed in an attempt to link the above steps into a coherent mechanism include the membrane model, the secondary structure model, the critical deprotonation model, the percolation model, the critical ionization model, and the stone wall model, to mention but a few. In the following sections, we briefly review the aspects of these models. 

The secondary structure model, proposed by Templeton et al., relates the secondary structures of novolacs [see Figs. 11.36(a) and (b)] to their dissolution behavior. The authors distinguished between structures where intermolecular bonds between novolac molecules predominate and those with predominantly intramolecular hydrogen bonds and they correlated these to dissolution behavior. They found that, for example, for novolacs made from p-cresol, the secondary structure of the resin brings the OH groups of the phenols together to such an extent that... 

Templeton, C.R. Szamanda, and A. Zampini, Dissolution kinetics of positive photoresists the secondary structure model, Proc. SPIE 771, 136 (1987). 

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